Nearly 2000 heart transplants are performed in the United States each year, and many other organs, such as lung, kidney, liver and pancreas, are transplanted into patients as well. There is a relatively stable population of about 16,000 to 20,000 heart transplant patients. Unfortunately, the average heart transplant patient survives only 8 to 10 years after receiving a transplant. New recipients, as well as the existing cohort of transplant recipients, need to be monitored for evidence of allograft rejection so that treatment can be administered as soon as possible. If transplant rejection is diagnosed relatively late, there is often significant tissue damage in the transplanted organ and hospitalization is almost inevitable. If the damage to the organ is extensive, a retransplant may also be required.
The current method for the monitoring and diagnosis of rejection after human cardiac transplant is invasive, and it entails the use of the transvenous myocardial bioptome to procure cardiac biopsy samples, which are then examined for histological evidence of rejection. A graded score of 0 to 4 is used; a score of 0 is assigned where there is no evidence of rejection and 4 is the maximum score of tissue damage and rejection. This pathology-graded score, together with clinical criteria, are used to institute immunosuppressive therapies for heart transplant patients with a diagnosis of rejection. By contrast, liver, kidney and lung transplants can be monitored by noninvasive enzymatic assays of urine and/or blood. However, in those cases, damage to the transplanted organ has occurred by the time diminished function is reflected in the tests, and the present invention provides an earlier method for diagnosis and/or prediction of rejection episodes.
The current method has certain other disadvantages in addition to being invasive. The greatest potential problem is sampling error due to the tendency of the bioptome to lodge in the same anatomic area of the heart. There is a small but real risk associated with the biopsy procedure, the procedure is costly, and there is a very high level of skill needed to perform the procedure.
Thus, there is a long-felt need in the art for a noninvasive, relatively inexpensive and accurate method for the assessment of the rejection state of a transplanted organ in a recipient patient.